REPORT
Clinical practice of procalcitonin and hypersensitive c-reactive protein
test in neonatal infection
Aimei Yao*, Jingyan Liu, Jing Chang, Caiyan Deng, Yulian Hu1, Fengqin Yu,
Zhanmin Ma and Guangzhou Wang
Maternal and Child Health Hospital of Zhengzhou City, Zhengzhou, Henan, China
Abstract: To study the clinical practice of procalcitonin and hypersensitive c-reactive protein test in neonatal infection.
Two hundred cases of our hospital treatment confirmed infection early newborn children were selected from February
2014 to March 2015. According to the condition, the children were divided into four groups as follows: severe infection
group, local infection group, non-infection group and healthy newborns group. At the same time, the new healthy
newborns were chosen as control group. The levels of serum procalcitonin and high-sensitivity C-reactive protein were
detected in all children and the levels in severe infection group children before and after treatment were also
quantitatively detected and the test results were analyzed. There was significant difference in procalcitonin among the
four groups (pS<0.05). The positive rate of the high-sensitivity C-reactive protein in local infection group has no
significant difference compared with the non-infection group (p>0.05). But there was significant difference between the
local infection group and healthy newborn group. As for the severe infection group, both the levels of procalcitonin and
positive rate of high-sensitivity C-reactive protein had significant difference compared with the other groups. The
detection of procalcitonin and high-sensitivity C-reactive protein could contribute to the diagnose of the early infection
neonatal children and has important values in diagnosis and treatment of infectious diseases in the newborns.
Keywords: Procalcitonin, Hypersensitive c-reactive protein, Pediatrics, Infection, Disease
INTRODUCTION
Newborn was easy to be infected with the bacterial
infectious disease owing to the low resistance and
immunity (Sanders et al., 2008). When the children
suffered from the disease, the signs and symptoms are
non-specific (Olaciregui et al., 2009). Moreover, the
development of the disease was quite quick and it had
severe damage to the children with the high case fatality
rate (Yo et al., 2012). Generally, the best treatment time
was usually lost due to the lack of reliable early diagnosis
index in clinical practice. So, early diagnosis has
important clinical value in the diagnosis of pediatric
neonatal diseases. At present, the detection of
procalcitonin and hypersensitive c-reactive protein were
widely used in the clinical diagnose of pediatric
examination (Youssef et al., 2007). In this paper, we
analyzed the application of procalcitonin and
hypersensitive c-reactive protein in the clinical diagnosis
of neonatal disease. The research was as follows.
MATERIAL AND METHOD
Materials
Two hundred cases of our hospital treatment children
were randomly selected from February 2014 to March
*Corresponding author: e-mail: zmabc2015@sina.com
Pak. J. Pharm. Sci., Vol.29, No.2(Suppl), March 2016, pp.753-756
2015. According to the condition, the children were
divided into four groups as follows: Severe infection
group, local infection group, non-infection group and
healthy newborns group The new healthy newborns were
chosen as control group. In severe infection group, there
were male children (26 cases) and female children (24
cases). The born time was 5-20d, average age was
(10.5±4.5) d. And there were 31 cases infected with
septicemia, 15 cases infected with severe pneumonia and
4 cases with necrotizing enteritis. In local infection group,
there were male children (27 cases) and female children
(23 cases). The born time was 5-20d, average age was
(9.5±5.0) d. There were 25 cases infected with
pneumonia, 14 cases infected with enteritis, 5 cases with
impetigo and 6 cases infected with omphalitis. As for the
non-infection group, there were male children (25 cases)
and female children (25 cases). The born time was 6-20 d,
average age was (10.8±4.5) d. Among these children,
there were jaundice (35 cases), allergic dermatitis (12
cases) and asphyxia (3 cases). For the healthy children,
there were male children (26 cases) and female children
(24 cases). The born time was 5-20 d, average age was
(11.0±4.0) d. There was no significant difference in
gender and age of the newborns in each group.
The diagnostic standards of severe infections
The diagnosis of severe infection group was based on the
clinical symptoms, imaging findings, laboratory
examination results and so on. The children who had
753
Clinical practice of procalcitonin and hypersensitive c-reactive protein test in neonatal infection
severe infection and systemic inflammatory response will
be diagnosed as severe infection children.
Testing method
The venous blood was collected from children before the
use of antibiotics for treatment. Then the levels of
procalcitonin and hypersensitive c-reactive protein were
detected and the blood bacterial culture were performed.
The value of procalcitonin was detected by Chemical
luminescence method using the French bioMerieux Mini
VIDAS along with the corresponding instruments and
reagents. The positive diagnostic criterion was >0.25
ng/ml. Immunofluorescence assay was performed to
detect the hypersensitive c-reactive protein. Test
instrument is i-CHROMA and the reagent used in the test
was produced by South Korea MedInc Boditech company.
The positive diagnostic criteria of C reactive protein was
>3mg/L. The levels of procalcitonin and hypersensitive creactive protein in severe infection group were tested
again after the children receiving treatment for 10 d.
STATISTICAL ANALYSIS
All data were assessed by SPSS 16.0 program. The
quantitative data was tested by T test and represented by
(x ±S). The enumeration data was tested by x2 test and
given by [n (%)]. Differences were considered to be
statistically significant at p<0.05.
RESULTS
The comparison of the serum concentrations of
procalcitonin and hypersensitive c-reactive protein in
each group
There were significant differences in serum
concentrations of procalcitonin and hypersensitive creactive protein for each group (p<0.05). Compared with
other groups, the testing results of severe group had
significant differences. While for the hypersensitive creactive protein detection, the results showed that there
was no significant difference between local infection
group and non-infection group with the p>0.05. But
compared with the healthy children group, the results had
significant difference. All the data were shown in table 1.
Studies have shown that the results of the detection of
hypersensitive c-reactive protein in bacterial infection is
significantly higher than that of non-bacterial infection.
Under normal circumstances, the content of
hypersensitive c-reactive protein in serum is very low,
when the bacteria invade the body by stimulating the
production of inflammatory, the peak concentration tens
to hundreds times of basic value.
The positive rate of the procalcitonin and hypersensitive
c-reactive protein in each group
The results showed that the positive rate of the
hypersensitive c-reactive protein had no significant
difference between local infection group and non-
754
infection group (p>0.05). But there was significant
difference compared with the healthy children group with
the p<0.05. As for the severe infection group, both the
positive rate of procalcitonin and hypersensitive creactive protein had significant difference compared with
the other groups (p<0.05). The results were revealed in
table 2.
Comparison of the levels of procalcitonin and
hypersensitive c-reactive protein in severe infection
group before and after treatment
The results revealed that the levels of procalcitonin and
hypersensitive c-reactive protein in severe infection group
had significant difference before and after treatment. The
results were shown in table 3. Procalcitonin levels were
significantly elevated when there were severe bacterial
infections and systemic manifestations. The procalcitonin
decreased after infection being controlled and it was only
slightly increased in viral infection and local bacterial
infection. It demonstrated that most of the calcitonin was
combined with the thyroid and other organs, which
indicated that it had better specificity and sensitivity to
bacterial pneumonia and mycoplasma pneumonia.
DISCUSSION
Infectious diseases seriously affect the health and safety
of newborn in pediatric clinical treatment and the
mortality rate caused by infectious diseases was
especially high (Zhang et al., 2014). Bacteria could
survive and multiply in the blood of newborns and
produce toxin constantly which would affect the safety of
newborns (O'Donnell, 2011). In pediatric clinical
treatment of neonatal infection, it was difficult to
diagnosis the disease because the children just suffer from
fever, poor response and other clinical manifestations,
which were not obvious (Yo et al., 2012). Therefore, it is
important to make the diagnosis and efficacy assessment
of neonatal infection disease to enhance the clinical
treatment.
Newborn was easy to be infected with the bacterial
infectious disease owing to the low resistance and
immunity (Gilsdorf, 2012). Based on the previous study,
the incidence of infectious diseases was 0.1-1%, but the
mortality rate was up to 15%-50% (Sachdev, 2004). In the
current
clinical
diagnosis,
procalcitonin
and
hypersensitive c-reactive protein were valued as the
observation index for the early diagnosis of newborn
infectious disease. Procalcitonin was mainly produced by
thyroid cells and it had no biological activity (Riedel,
2012). However, the children’s lung, liver, endocrine cells
would also produce procalcitonin when the newborn was
infected. Hypersensitive c-reactive protein is synthesized
by liver and is thought to be the inflammatory index due
to the higher sensitivity in the clinical diagnosis (Sanders
et al., 2008).
Pak. J. Pharm. Sci., Vol.29, No.2(Suppl), March 2016, pp.753-756
Aimei Yao et al
Table 1: The comparison of the serum concentrations of procalcitonin and hypersensitive c-reactive protein in each
group
Groups
Severe infection group
Local infection group
Non-infection group
Healthy group
Procalcitonin (ng/ml)
8.5±7.1*&#
2.3±1.0*&
0.7±0.4*
0.3±0.2
Hypersensitive c-reactive protein(ng/ml)
37.5±15.6*&#
18.5±6.2*
17.1±15.9*
3.5± 0.8
Table 2: The positive rate of the procalcitonin and hypersensitive c-reactive protein in each group [n (%)]
Groups
Severe infection group
Local infection group
Non-infection group
Healthy group
Cases
50
50
50
50
Procalcitonin (ng/ml)
45(90.00)
34(68.00)
6(12.00)
3(6.00)
Hypersensitive c-reactive protein (ng/ml)
31(62.00)
22(44.00)
20(40.00)
2(4.00)
Note: Compared with control group, *p<0.05; Compared with non-infection group, & p<0.05;compared with local infection group,
#p<0.05
Table 3: Comparison of the levels of procalcitonin and hypersensitive c-reactive protein in severe infection group
before and after treatment
Before the treatment
After the treatment
T
P
Procalcitonin (ng/ml)
8.5±7.1
1.1±0.4
7.3582
0.0000
In this study, we analyzed the levels of procalcitonin and
hypersensitive c-reactive protein in the blood of severe
infection, local infection, non-infection and normal
healthy children. The number of positive cases in each
group was 45,34,6 and 3 cases for procalcitonin and 31,
22, 20, 2 cases for hypersensitive c-reactive protein,
respectively. The results showed that the levels of
procalcitonin and hypersensitive c-reactive protein in the
blood of severe infection group were even up to (37.5),
(8.5) before the treatment. However, the data were
separately after treatment which indicated that the content
of procalciton in the serum of severe infection group was
relatively high and it also demonstrated the sharp increase
of the procalciton in the serum was closely related to the
infection. In this study, the content of procalcitonin and
hypersensitive c-reactive protein in the serum of
newborns were as follows: Severe infection group > local
infection group > non-infection group > healthy group.
The main reason for the increase of the procalcitonin was
that the patient's thyroid system will occur lesions when
the patients were infected with the bacteria and viruses. It
would result in the release of thyroid cells to increase the
amount of procalcitonin, thereby increasing the
concentration of the procalcitonin in the patients’ blood.
Hypersensitive c-reactive protein is an acute phase protein
synthesized by the liver. It is found in the serum of
patients with acute inflammation and secreted by the liver
Pak. J. Pharm. Sci., Vol.29, No.2(Suppl), March 2016, pp.753-756
Hypersensitive c-reactive protein (ng/ml)
37.5±15.6
9.5±3.1
12.4483
0.0000
in the inflammatory stimulation. It is regulated and
induced by many cytokines, such as IL-I, IL-6, TNF-, etc.
which were also the nonspecific markers of inflammation.
Hypersensitive c-reactive protein was generated by the
liver which was stimulated by the activation of
neutrophils and macrophages such as leukocyte
interleukin -6 in the acute stage of inflammatory
cytokines. The levels of hypersensitive c-reactive protein
began to rise in several hours and reach peak during 48
hours. It returned to normal with the lesions subsided.
Hypersensitive c-reactive protein was not affected by the
factors of age, sex, body temperature and anemia, so it is
considered to be a preferred index for the distinguish of
bacterial infection and viral infection. The hypersensitive
c-reactive protein can activate the complement system of
the organism after binding to the protein on the cell wall
of the pneumococcal cell, and promote the process of
humoral immune cell immunity and other immune
regulation. But the increasing trend of hypersensitive creactive protein in the virus infection is usually not
significant. Compared with the children who had
mycoplasma pneumonia, viral pneumonia and healthy
children, the levels of hypersensitive c-reactive protein
were significantly increased in the children who had
bacterial pneumonia. In all, the levels of hypersensitive creactive protein were respectively bacterial pneumonia in
children > mycoplasma pneumonia in children > virus
pneumonia in children> healthy children. Therefore, the
hypersensitive c-reactive protein is one of the important
755
Clinical practice of procalcitonin and hypersensitive c-reactive protein test in neonatal infection
indicators for the differential diagnosis of early infection
in children with pneumonia.
Related studies have shown that the levels of
procalcitonin would increase when the patients suffer
from the systemic infection. It might be explained by the
reason that the patients’ other organs also released the
procalcitonin expect the thyroid cells (Tay et al., 2006). It
had been confirmed that stem cells would produce a large
number of procalcitonin in the induction of tumor
necrosis (Smith et al., 2006). However, the peripheral
blood mononuclear cells are the main sites of the
production of calcitonin and the content of procalcitonin
would increase significantly in the stimulation of
lipopolysaccharide.
The procalcitonin is a glycoprotein consisting of 116
amino acids and precursor peptide of calcitonin without
the active hormone calcitonin. It was found that the
selective induction of elevated procalcitonin was
associated with high sensitivity and specificity for
bacterial infections and was proportional to the severity of
the disease. In chronic renal failure (CRF), inhalation
injury, acute bacterial infections, and other non-thyroid
injury, serum procalcitonin level has increased to a certain
degree, some even increased exponentially which
indicated that there are still other cells secreting and
storaging procalcitonin except for medullary thyroid cells.
Related research found that the increasing of the original
value of procalcitonin is usually not obvious. But when
the body suffered from severe infection (such as bacteria,
fungi or parasites infection) and had systemic
manifestations, calcitonin hormone levels will be
increased significantly. The study showed that the main
cause of the induced procalcitonin was the response of the
organism to the bacterial endotoxin.
Generally speaking, the content of hypersensitive creactive protein in the blood of healthy people was
relatively low, but in this study we found that the level
was especially high in the serum of the severe infection,
local infection and non-infection patients. The results
revealed that the concentration of hypersensitive creactive protein would increase dramatically as soon as
the patients were infected with bacteria or within 6-12h.
After being infected for 24-28h, the levels would reach
the maximum which were even hundreds of times or
thousands of times of the normal person. And the
concentration would decrease as soon as the infection or
inflammation alleviate. Compared with the other related
studies, our results about the content of hypersensitive creactive protein in the serum of patients had no significant
difference. It proved that our study is of great significance
and the level of hypersensitive c-reactive protein could be
used as an early diagnostic index for the diagnosis of
pediatric infections.
756
In this paper, our results showed that the levels of
procalcitonin and hypersensitive c-reactive protein were
of great importance for the clinical diagnosis. It could
help to diagnose, monitor the disease and enhance the
accuracy of diagnosis, so the detection of procalcitonin
and hypersensitive c-reactive protein could be widely
applied to the clinical diagnosis of pediatric patients.
REFERENCES
Gilsdorf JR (2012). C-reactive protein and procalcitonin
are helpful in diagnosis of serious bacterial infections
in children. TJP, 160: 173-174.
O'Donnell DR (2011). A scoring model including
procalcitonin, C-reactive protein and urinalysis is
superior to individual variables in detecting serious
bacterial infection in children under three years old.
TJP, 158: 862-863.
Olaciregui I, Hernandez U, Munoz JA, Emparanza JI and
Landa JJ (2009). Markers that predict serious bacterial
infection in infants under 3 months of age presenting
with fever of unknown origin. ADC, 94: 501-505.
Riedel S (2012). Procalcitonin and the role of biomarkers
in the diagnosis and management of sepsis. DMID, 73:
221-227.
Sachdev P (2004). Homocysteine, cerebrovascular disease
and brain atrophy. JNS, 226: 25-29.
Sanders S, Barnett A, Correa-Velez I, Coulthard M and
Doust J (2008). Systematic review of the diagnostic
accuracy of C-reactive protein to detect bacterial
infection in nonhospitalized infants and children with
fever. TJP, 153: 570-574.
Smith CJ, Emsley HC, Vail A, Georgiou RF, Rothwell NJ,
Tyrrell PJ and Hopkins SJ (2006). Variability of the
systemic acute phase response after ischemic stroke.
JNS, 251: 77-81.
Tay SY, Ampil ER, Chen CP and Auchus AP (2006). The
relationship between homocysteine, cognition and
stroke subtypes in acute stroke. JNS, 250: 58-61.
Yo CH, Hsieh PS, Lee SH, Wu JY, Chang SS, Tasi KC
and Lee CC (2012). Comparison of the test
characteristics of procalcitonin to C-reactive protein
and leukocytosis for the detection of serious bacterial
infections in children presenting with fever without
source: A systematic review and meta-analysis. AEM,
60: 591-600.
Youssef MY, Mojiminiyi OA and Abdella NA (2007).
Plasma concentrations of C-reactive protein and total
homocysteine in relation to the severity and risk factors
for cerebrovascular disease. TR:TJLCM, 150: 158-163.
Zhang X, Huang WJ and Yu ZG (2014). Relationship
Between the Hypersensitive c-Reactive Protein (hsCRP) Level and the Prognosis of Acute Brainstem
Infarction. CBB, 145: 321-343.
Pak. J. Pharm. Sci., Vol.29, No.2(Suppl), March 2016, pp.753-756